I obtained my degree of Biology at the University of Buenos Aires, Argentina, in 2005. I worked on breast cancer research from 2003 to 2010, when I obtained my PhD at the University of Buenos Aires. I joined Dr Ari Melnick's lab at WCMC in 2010, where I am working in the field of lymphoma epigenetics.

B-cell lymphomas are the fourth most common malignancy in the USA and many patients are not cured with existing therapies. Most lymphomas arise from germinal center (GC) B-cells, which are uniquely specialized to simultaneously proliferate and tolerate the DNA damage occurring as a byproduct of immunoglobulin affinity maturation. Upon activation, GC B-cells markedly upregulate EZH2, a histone H3K27 methyltransferase component of Polycomb PRC2 complex in both the nucleus and cytoplasm. EZH2 mediates epigenetic silencing of GC B cell specific genes through its H3K27 methylation activity, including several key tumor suppressor genes. EZH2 and PRC2 also have cytoplasmatic functions, regulating signal transduction and actin polymerization. A majority of B-cell lymphomas express EZH2, and somatic heterozygous Y641 point mutations in the EZH2 SET (catalytic) domain were recently identified in DLBCL and FL (the most common lymphomas). These mutations cause EZH2 to preferentially trimethylate H3K27, whereas wild type EZH2 preferentially catalyzes mono- and dimethylation. The fact that tumor cells retain the wild type allele further underline the fact that the function of wild type vs. mutant EZH2 do not entirely overlap thus suggesting a unique gain of function in regulation of gene expression and/or cytosolic signaling. Our studies are revealing how EZH2 contributes to the GC B-cell phenotype and lymphomagenesis, how transformation may be accelerated by EZH2 Y641 mutation, and the role of EZH2-targeted therapy as a modality to improve lymphoma treatments.